Estradiol Regulation of Constitutive and Keratinocyte Growth Factor-Induced CCL20 and CXCL1 Secretion by Mouse Uterine Epithelial Cells

Abstract

Estradiol can directly affect epithelial cells or indirectly affect epithelial cells via stromal fibroblast secretion of growth factors, such as keratinocyte growth factor (KGF). The purpose of the present study was to determine whether estradiol regulates constitutive as well as KGF-induced uterine epithelial cell secretion of CCL20 and CXCL1. Freshly isolated and polarized uterine epithelial cells from Balb/c mice were cultured with estradiol in the presence or absence of KGF. CCL20 and CXCL1 were measured by ELISA. Estradiol inhibited CCL20 secretion by freshly isolated and polarized uterine epithelial cells in the presence or absence of KGF. Unexpectedly, it enhanced KGF-induced CXCL1 secretion beyond that seen with KGF alone. Estradiol increased CXCL1 secretion at 24 hr and inhibited CCL20 at 48 hr. The effects of estradiol are specific in that progesterone, cortisol, dihydrotestosterone, and aldosterone had no effect on either CCL20 or CXCL1 secretion. The inhibitory effect of estradiol on CCL20 secretion was reversed with ICI 182,780, an estrogen receptor antagonist, indicating that this effect is estrogen receptor mediated. Our data indicate that estradiol is important in regulating the effects of KGF on mouse uterine epithelial cell secretion of CCL20 and CXCL1.